A living body continuously introduces a foreign material (i.e., an antigen material) to the inside of the body by physiological actions like breathing or eating that are essential for maintaining biological activities. As a result, surface of a respiratory organ or a digestive tract of a living body is constantly exposed to an antigen material and bacteria or viruses, and allergens originating from pollen and food, etc. having a pathogenic property may be included therein. In other words, on the surface of a respiratory organ or a digestive tract, a living body remains constantly exposed to pathogenic microorganisms and allergens.
Accordingly, in response to various invading antigen materials, a living body has an immune response system which can distinguish favorable ones from unfavorable ones and exclude them depending on necessity. The immune system found on the surface of a respiratory organ or a digestive tract as a front-end defense mechanism is mucosal immune.
As a key player for the mucosal immune system, the material responsible for preventing attachment of pathogenic microorganisms or invasion and absorption of allergens to a living body is immunoglobulin A (hereinafter, also referred to as “IgA”), which is one type of immunoglobulins.
IgA plays an important role of neutralizing bacteria or viruses, inhibiting their attachment to biological tissues, and inhibiting allergy caused by food antigen, etc., and as an IgA-inducing tissue, Peyer's patch is present in an intestinal canal.
It is known that babies, elderly and people with poor health have a weak immunity, and therefore exhibit low resistance to foreign materials from the outside like pathogens. In addition to this, it is also reported that humans nowadays have a reduced enteric mucosal immune due to stress caused by a change in living environments, etc., and as a result allergic diseases are dramatically increased (Non-Patent Document 1).
Thus, if IgA production from mucosa of a living body is enhanced, immunity on the surface of mucosa of an intestinal canal, etc. can be increased, and therefore it is expected that infection by pathogenic microorganisms or occurrence of allergic reaction can be effectively prevented.
Meanwhile, under the purpose of providing an animal protein to human beings, in the field of livestock farming, livestock is raised as an animal with an economical benefit, and a raising style which values so-called productivity like increasing body weight or enhancing maturity, etc. has been conventionally adopted. In addition to the purpose of enhancing the productivity, vaccination or addition of antibiotics to animal feeds has been actively carried out to prevent an outbreak of diseases, etc from the view point of enhancing hygiene level of a livestock product as a food.
In recent years, in addition to the raising style described above, stockbreeding management is transformed into large-scale management form which pursues an economic value according to efficiencies obtained from mechanization and a scale merit by raising a great number of animals.
Thus, although the recent livestock management made it possible to provide stable supply of low-price livestock products to consumers, it is also true that the livestock is put into a stressful environment like less area for breeding and more possibilities of vaccination.
In addition to the situations described above, secondary infection by bacteria like E. coli increases now more than ever in current livestock breeding due to the emergence of pathogenic viruses which inhibit an immune function of a living body (Non-Patent Document 2).
In livestock breeding, occurrence of a disease like diarrhea causes an increase in accident rate or a reduction in body weight gain, therefore yielding low productivity. In particular, since young animals are prone to suffer from diseases and it results in a significant economic loss, it is important to prevent the occurrence of disease as much as possible. In this regard, the use of antibiotics is rather limited due to the concern regarding the emergence of antibiotic-resistant bacteria, etc. Thus, as a measure for dealing with the frequent diseases, the use of antibiotics is now very carefully considered by livestock breeders. In this connection, it is now livestock breeders' wish to have the development of animal feeds or feed additives having an antibiotic-like activity that are originated from natural products and can replace antibiotics.
In order to solve the above problems, it would be very useful if a substance which is safe and has an activity of increasing immunity of a living body and enhancing resistance is found from natural products and is used as food products, animal feeds or pharmaceutical agents. In this regard, since IgA is a substance which plays a key role in immunological mechanism on surface of mucosa, it is desired to develop food products or animal feeds which can increase the production amount of IgA and activate the immunity of a living body.
Meanwhile, it has long been known that the lactic acid bacteria have probiotic effects. As one of the effects, it is known that the bacteria body has an immunostimulating effect (Non-Patent Document 3).
In the field of livestock breeding, many studies are being carried out based on the idea that the immunostimulating effects of the lactic acid bacteria can increase resistance against diseases (Non-Patent Document 7).
As for the lactic acid bacteria which can induce IgA production, that is one of the immunostimulating effects, there are reports regarding Bifidus bacteria in addition to the lactic acid bacteria belonging to the genus Lactobacillus, the genus Leuconostoc and the genus Pediococcus originating from a plant (Patent Documents 1 and 2) or Enterococcus bacteria (Patent Documents 3 to 5).
It can be generally said that colonization rate of the lactic acid bacteria originating from a plant is not high in a body of an animal like human. Further, being an obligate anaerobe, Bifidus bacteria need a special environment for culture condition, i.e., anaerobic culture. In addition, there are also bacterium strains which require nutrients like special amino acids, vitamins and metal ions as a component for medium, and therefore the artificial culture medium becomes to have a complicate composition (Non-Patent Document 4). In addition, as being an obligate anaerobe, they cannot grow under normal environmental condition having oxygen, and there is also a problem in viability and stability when prepared in a preparation.
Meanwhile, the lactic acid bacteria belonging to the genus Enterococcus are the lactic acid bacteria which are present in the gut of mammals. Being a facultative anaerobe, they do not require special culture condition like Bifidus bacterium and are suitable for large-scale culture as they are a bacterial species which can propagate in a medium having relatively simple composition. Furthermore, as the culture in the presence of oxygen is possible, their viability and stability under normal environmental condition are higher than those of Bifidus bacterium. Furthermore, considering that they are the lactic acid bacteria which are originally present in the gut of mammals, it is expected that they have higher colonization rate than other lactic acid bacteria originating from a plant when they are orally administered to a human or an animal.
In addition, it has been already known that some bacterium strains of the Enterococcus bacteria have immunostimulating effects and are used as an agent for preventing infections against microbes having resistance to pharmaceutical agents (Patent Documents 3 to 5) and the bacterium strains having immunostimulating effects according to increased production of IgA have been reported (Patent Document 5), and also an immunostimulating agent, an anti-cancer agent and various preparations for allergy are suggested.
However, the lactic acid bacteria belonging to the genus Enterococcus as used in the lactic acid bacterium preparation of Patent Document 5 are Enterococcus faecalis and the production amount of IgA induced by the bacterium strain is less than twice the negative control, which cannot be said to be sufficient.
Enterococcus faecium, which is one type of the bacteria belonging to the genus Enterococcus, is a bacterial species that has been conventionally and widely used as a medicine for intestinal disorders or an additive for animal feeds. Thus, based on the fact that it has no problem in terms of safety and enteric colonization and the technology required for the large scale culture has been already established, if it becomes possible to use it as a lactic acid bacterium preparation having immunostimulating effects for pharmaceutical products, food products or animal feeds, it is believed to be one of the hopeful lactic acid bacteria being extremely useful from the economical point of view, as well as the safety and immune function enhancing effects described above.
However, until now there is almost no report regarding the induction of IgA production in Enterococcus faecium. Although Patent Documents 6 and 7 describe that Enterococcus faecium has an activity of inducing IgA production, the one that is actually determined as an activity of inducing IgA production is an indirect determination based on a property change in Peyer's patch (i.e., IgA antibody). Thus, no quantitative determination on effectiveness is made and also it cannot be said that the IgA production-inducing ability itself is sufficient.
Furthermore, regarding any of the lactic acid bacteria of the genus Enterococcus described above, no determination was made on the immunostimulating effects that are based on the effect of inhibiting colonization of pathogenic substances or the effect of increasing productivity of livestock, and therefore verification of the effectiveness is insufficient.
[Patent Document 1] Japanese Patent Application Laid-Open (JP-A) No. 2007-308419
[Patent Document 2] JP-A No. 2-280059
[Patent Document 3] Japanese Patent No. 3151442
[Patent Document 4] JP-A No. 2006-89421
[Patent Document 5] JP-A No. 11-92389
[Patent Document 6] JP-A No. 2003-113114
[Patent Document 7] JP-A No. 2006-67881
[Non-Patent Document 1] “Front line of the mucosal immunology,” Yasunobu Yoshikai ed., pages 116 to 129, published by Medicinal and Dental Journal Publications
[Non-Patent Document 2] “Measures for swine disease in actual field,” written by Hiromichi Ishikawa, pages 13 to 16, published by Benet, Ltd.
[Non-Patent Document 3] “Intestinal flora and infection•immunity,” Tomotari Mitsuoka ed., pages 156 to 158, published by Publication center of the academic society
[Non-Patent Document 4] “Sciences of fermented milk,” Akiyoshi Hosono ed., pages 217 to 223, published by I•K corporation
[Non-Patent Document 5]Yakugaku Zasshi, Vol. 112, No. 12, pages 919 to 925, 1992
[Non-Patent Document 6]Modern media, Vol. 52, No. 7, pages 209 to 216, 2006
[Non-Patent Document 7] “Health functions and applications of lactic acid bacteria,” reviewed by Shuichi Kaminogawa, pages 306 to 312, CMC publications